title: Lamivudine-resistant HBV strain rtM204V/I in acute hepatitis B.
abstract: OBJECTIVE
  To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance.
  
  
  METHODS
  Eighty HBV DNA-positive patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR).
  
  
  RESULTS
  No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p < 0.05) and lower values of serum HBV DNA (1.77 × 10(6) ± 4.76 × 10(6) vs. 1.68 × 10(8) ± 5.46 × 10(8)). In addition, a multivariate analysis identified the presence of a pre-existing HCV chronic infection as independently associated with severe acute hepatitis B (p < 0.05).
  
  
  CONCLUSIONS
  HBV rtM204V/I lamivudine-resistant strains were detected in serum of 11 (13.7%) patients with acute hepatitis B by allele-specific polymerase chain reaction. The frequent association of rtM204V/I with a more severe acute hepatitis B and with a lower viral load may suggest that greater and/or more prolonged immune pressure might have induced their selection.
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.forename: Gilda
authors.initials: G
authors.lastname: Tonziello
authors.forename: Piero
authors.initials: P
authors.lastname: Colombatto
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Pisaturo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Messina
authors.forename: Francesco
authors.initials: F
authors.lastname: Moriconi
authors.forename: Loredana
authors.initials: L
authors.lastname: Alessio
authors.forename: Caterina
authors.initials: C
authors.lastname: Sagnelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Cavallone
authors.forename: Maurizia
authors.initials: M
authors.lastname: Brunetto
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007558:Italy; D019259:Lamivudine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase
keywords: ALT; AST; AVH-B; Acute hepatitis B; Alanine aminotransferase; Aspartate aminotransferase; HBV; HBsAg; IgM to hepatitis B core antigen; Lamivudine; Mutant HBV strains; PCR; Resistance to nucleos(t)ide analogues; acute viral hepatitis B; anti-HBc IgM; anti-HDV; antibodies to hepatitis D virus; hepatitis B Virus; hepatitis B surface antigen; polymerase chain reaction; rtM204I; rtM204V